Using various exposure conditions, we studied the induction of DNA-protein crosslinks (DPX) by formaldehyde (FA) and their removal in primary human nasal epithelial cells (HNEC). DPX were indirectly measured by the alkaline comet assay as the reduction of gamma ray-induced DNA migration. DPX are the most relevant primary DNA alterations induced by FA and the comet assay is a very sensitive method for the detection of FA-induced DPX. In parallel experiments, we investigated changes in gene expression by using a full-genome human microarray. After a single treatment with FA (50-200muM), concentration- and time-dependent changes in gene expression were seen under conditions that also induced genotoxicity. Repeated treatments with low FA concentrations (20 and 50muM) did not lead to a significant induction of DPX but repeated treatments with 50muM FA changed the expression of more than 100 genes. Interestingly, altered expression of genes involved in the main pathways for FA detoxification and the repair of DPX were not specifically detected.
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